Embolic coils and related components, systems, and methods

ABSTRACT

The present invention relates generally to systems and methods for delivering embolic devices into a body lumen of a patient. These embolic devices are applicable to a variety of neurological and/or peripheral applications. In particular, the embolic devices may be used to occlude a vessel within a patient, and/or to treat aneurysms, arteriovenous malformations, traumatic fistulas, uterine fibroids or cancer.

TECHNICAL FIELD

The invention relates to embolic coils, and related components, systems,and methods.

BACKGROUND

Therapeutic vascular occlusions (embolizations) are used to prevent ortreat pathological conditions in situ. Embolic coils can be used toocclude vessels in a variety of medical applications. Delivery ofembolic coils (e.g., through a catheter) can depend on the size and/orshape of the coils. Some embolic coils include fibers that can, forexample, enhance thrombosis at a treatment site.

SUMMARY

In one aspect, the invention features an article that includes anembolic coil and a non-hook-shaped head attached to the embolic coil.

In another aspect, the invention features an embolic coil delivery wirehaving a non-hook-shaped head.

In an additional aspect, the invention features an article that includesan embolic coil delivery wire and at least two arms extending from theembolic coil delivery wire.

In a further aspect, the invention features an article that includes anembolic coil and at least two arms extending from the embolic coil.

In another aspect, the invention features an article that includes afirst coiled wire and a second coiled wire that is co-wound with thefirst coiled wire. The article is an embolic coil.

In an additional aspect, the invention features an embolic coil systemthat includes a catheter having a lumen and an article disposed in thelumen of the catheter. The article includes an embolic coil and anon-hook-shaped head attached to the embolic coil.

In a further aspect, the invention features an embolic coil system thatincludes a catheter having a lumen and an embolic coil delivery wiredisposed in the lumen of the catheter. The embolic coil delivery wirehas a non-hook-shaped head.

In another aspect, the invention features an embolic coil system thatincludes a catheter having a lumen, an embolic coil delivery wiredisposed in the lumen of the catheter, and at least two arms extendingfrom an end of the embolic coil delivery wire.

In an additional aspect, the invention features an embolic coil systemthat includes a catheter having a lumen and an article disposed in thelumen of the catheter. The article includes an embolic coil and at leasttwo arms extending from the embolic coil.

In a further aspect, the invention features an article that includes anembolic coil delivery wire and a tubular mesh member attached to theembolic coil delivery wire.

In another aspect, the invention features a method that includesdelivering an embolic coil system into a body of a subject. The emboliccoil system includes a catheter having a lumen and an article disposedin the lumen of the catheter. The article includes an embolic coil and anon-hook-shaped head attached to the embolic coil.

In an additional aspect, the invention features a method that includesdelivering an embolic coil system into a body of a subject. The emboliccoil system includes a catheter having a lumen and an embolic coildelivery wire disposed in the lumen of the catheter. The embolic coildelivery wire has a non-hook-shaped head.

In a further aspect, the invention features a method that includesdelivering an embolic coil system into a body of a subject. The emboliccoil system includes a catheter having a lumen, an embolic coil deliverywire disposed in the lumen of the catheter, and at least two armsextending from an end of the embolic coil delivery wire.

In another aspect, the invention features a method that includesdelivering an embolic coil system into a body of a subject. The emboliccoil system includes a catheter having a lumen and an article disposedin the lumen of the catheter. The article includes an embolic coil andat least two arms extending from the embolic coil.

In an additional aspect, the invention features a method that includesdelivering an embolic coil system into a body of a subject. The emboliccoil system includes an embolic coil delivery wire, at least two armsextending from the embolic coil delivery wire, and an embolic coil thatis detachably engaged with the arms. The method also includes detachingthe embolic coil from the arms of the embolic coil system.

In a further aspect, the invention features a method that includesdelivering an embolic coil system into a body of a subject. The emboliccoil system includes an embolic coil delivery wire having anon-hook-shaped head, and an embolic coil that is detachably engagedwith the non-hook-shaped head. The method also includes detaching theembolic coil from the non-hook-shaped head.

In another aspect, the invention features a method that includesdelivering an embolic coil system into a body of a subject. The emboliccoil system includes a catheter including a sheath having a lumen, anembolic coil delivery wire disposed in the lumen of the sheath, atubular mesh member attached to the embolic coil delivery wire, and anembolic coil that is at least partially disposed in a lumen of thetubular mesh member. The method also includes retracting the sheath sothat the sheath releases the embolic coil.

Embodiments can also include one or more of the following.

The head can have a longitudinal axis, and can be rotationally symmetricabout the longitudinal axis. In some embodiments, the head can bepeanut-shaped. The head can have a lumen and/or a groove. The emboliccoil delivery wire can include a body, and the head can be attached tothe body or can be integrally formed with the body.

The arms can be attached to a distal portion of the embolic coildelivery wire. The arms can be adapted to flex. The arms can form aninterference fit within the lumen of the catheter. The arms can beformed of the same material as the embolic coil delivery wire. Thearticle can have an end that includes an arm formed from the firstcoiled wire and an arm formed from the second coiled wire.

The embolic coil system can include an article including an embolic coildelivery wire that is detachably engaged with the non-hook-shaped head.The article can also include at least two arms extending from theembolic coil delivery wire. At least one of the arms can be detachablyengaged with the head of the embolic coil.

The embolic coil system can include an article including an emboliccoil, and the article can be detachably engaged with the head of theembolic coil delivery wire. The article can also include at least twoarms extending from the embolic coil. At least one of the arms can bedetachably engaged with the head of the embolic coil delivery wire.

The embolic coil system can include an embolic coil, and the arms can bedetachably engaged with the embolic coil.

The article can include an embolic coil. The tubular mesh member canhave a lumen, and the embolic coil can be at least partially disposed inthe lumen of the tubular mesh member. In certain embodiments, theembolic coil can have a non-hook-shaped head that is disposed in thelumen of the tubular mesh member.

Embodiments can include one or more of the following advantages.

In some embodiments, an embolic coil or an embolic coil delivery wirecan be adapted for use in delivery devices of different sizes. Forexample, in certain embodiments, an embolic coil delivery wire withmultiple arms extending from it can be adapted for use in microcathetershaving different inner diameters. In some embodiments, the arms can flexto allow the embolic coil delivery wire or the embolic coil to fitwithin a lumen of a delivery device (e.g., a catheter).

In certain embodiments, an embolic coil delivery wire with multiple armsextending from it can have enhanced rotational and/or axial flexibilityrelative to an embolic coil delivery wire that does not have multiplearms extending from it. This enhanced rotational and/or axialflexibility can, for example, allow the embolic coil delivery wire torelatively easily and/or precisely deliver an embolic coil to a targetsite. In some embodiments, the embolic coil delivery wire can be used tomanipulate an embolic coil into a desired position (e.g., by rotatingthe arms) prior to releasing the embolic coil into a target site.

In certain embodiments, an embolic coil having a non-hook-shaped headcan be relatively easy to maneuver and/or to deliver to a target site.As an example, the embolic coil can be detachably engaged with anembolic coil delivery wire (e.g., an embolic coil delivery wire withmultiple arms extending from it), which can be used to precisely placethe embolic coil at a target site. In some embodiments, after theembolic coil is delivered to a first site, the embolic coil deliverywire can be used to withdraw the embolic coil from the site and tore-position the embolic coil at a second site. The maneuverability ofthe embolic coil can, for example, allow the embolic coil to berelatively easily packed into a target site.

In certain embodiments, an embolic coil system including a catheter andan embolic coil delivery wire having arms that are engaged with a headof an embolic coil can be used to deliver the embolic coil to a targetsite relatively easily and/or efficiently. As an example, in someembodiments, the embolic coil system can experience relatively littlefriction between the embolic coil and the walls of the catheter duringdelivery of the embolic coil to a target site. As another example, incertain embodiments, the embolic coil system can be used to deliver theembolic coil to a target site without resulting in significantdeformation of the shape of the embolic coil. As an additional example,in some embodiments, the embolic coil can assume its secondary shaperelatively easily as the embolic coil is being delivered from thecatheter.

In some embodiments, an embolic coil having a non-hook-shaped head canbe sufficiently radiopaque to be viewed (e.g., by a physician and/or atechnician), for example, using X-ray fluoroscopy without using aradiopaque contrast agent. Such an embolic coil may be viewed using anon-invasive technique, and/or may be monitored to determine theprogress of a procedure. In certain embodiments, such an embolic coilcan be monitored to determine whether the embolic coil is migrating to asite that is not targeted for treatment.

Features and advantages are in the description, drawings, and claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a side view in partial cross-section of an embodiment of anembolic coil system.

FIGS. 2A and 2B illustrate the delivery of an embodiment of an emboliccoil to the site of an aneurysm.

FIG. 3A is a side view of an embodiment of an embolic coil deliverywire.

FIG. 3B is a cross-sectional view of the embolic coil delivery wire ofFIG. 3A, taken along line 3B-3B.

FIG. 4 is a side view of an embodiment of an embolic coil delivery wire.

FIG. 5A is a side view of an embodiment of an embolic coil.

FIG. 5B is a cross-sectional view of the embolic coil of FIG. 5A, takenalong line 5B-5B.

FIG. 6 is a perspective view of an embodiment of an embolic coil.

FIG. 7 is a perspective view of an embodiment of an embolic coil.

FIG. 8 is a perspective view of an embodiment of an embolic coil.

FIG. 9 is a perspective view of an embodiment of an embolic coil.

FIG. 10A is a front view of an embodiment of an embolic coil.

FIG. 10B is a side view of the embolic coil of FIG. 10A.

FIG. 11A is a front view of an embodiment of an embolic coil.

FIG. 11B is a side view of the embolic coil of FIG. 11A.

FIG. 12 is a side view of an embodiment of an embolic coil.

FIG. 13 is a side view of an embodiment of a process for forming anembolic coil.

FIG. 14A is a side view of an embodiment of a mandrel.

FIGS. 14B and 14C are illustrations of an embodiment of a process forforming an embolic coil using the mandrel of FIG. 14A.

FIG. 15A is a side view in partial cross-section of an embodiment of anembolic coil system.

FIG. 15B is a side view of an embolic coil delivery wire of the emboliccoil system of FIG. 15A.

FIG. 15C is a cross-sectional view of the embolic coil delivery wire ofFIG. 15B, taken along line 15C-15C.

FIG. 15D is a side view of an embolic coil from the embolic coil systemof FIG. 15A.

FIG. 15E is a cross-sectional view of the embolic coil of FIG. 15D,taken along line 15E-15E.

FIG. 16 is a side view of an embodiment of an embolic coil system.

FIG. 17 is a side view in partial cross-section of an embodiment of anembolic coil system.

FIGS. 18A-18C illustrate the delivery of an embodiment of an emboliccoil from an embodiment of an embolic coil system.

FIG. 19 is a side view of an embodiment of an embolic coil.

FIG. 20 is a side view in partial cross-section of an embodiment of anembolic coil system.

FIG. 21 is a side view of an embodiment of an embolic coil system.

FIG. 22 illustrates the delivery of an embodiment of an embolic coilfrom an introducer sheath into a delivery device.

DETAILED DESCRIPTION

FIG. 1 shows an embolic coil system 10, which includes a catheter 12with a lumen 14. An embolic coil delivery wire 16 and an embolic coil 18that is detachably engaged with embolic coil delivery wire 16 are bothdisposed within lumen 14. Embolic coil 18 includes an embolic coil body20 that is formed out of windings (e.g., windings 22, 23, 24, and 26) ofa wire 28. Embolic coil body 20 has a proximal end 30 and a distal end32. Embolic coil 18 also includes a non-hook-shaped head (as shown, apeanut-shaped head 34) that is attached to proximal end 30 of emboliccoil body 20. Two arms 36 and 38 extend from the distal end 40 ofembolic coil delivery wire 16. Arms 36 and 38, which are detachablyengaged with head 34 of embolic coil 18, form an interference fit withinlumen 14 of catheter 12. In some embodiments, when embolic coil deliverywire 16 and embolic coil 18 are disposed within lumen 14 of catheter 12,a fluid (e.g., a saline solution, a contrast agent, a heparin solution)can also be disposed within lumen 14.

Arms 36 and 38 are capable of flexing, such that they can fit within thelumens of catheters having a range of different inner diameters. Asshown in FIG. 1, catheter 12 has an inner diameter ID1 and an outerdiameter OD1. In some embodiments, inner diameter ID1 can be at least0.018 inch (e.g., at least 0.021 inch, at least 0.027 inch, at least0.03 inch) and/or at most 0.035 inch (e.g., at most 0.03 inch, at most0.027 inch, at most 0.021 inch). As an example, in certain embodiments,inner diameter ID1 can be 0.021 inch. An example of a catheter having aninner diameter of 0.021 inch is the Renegade® 18 Microcatheter (fromBoston Scientific Corp.). As another example, in some embodiments, innerdiameter ID1 can be 0.027 inch. An example of a catheter having an innerdiameter of 0.027 inch is the Renegade® Hi-Flo™ Microcatheter (fromBoston Scientific Corp.). In certain embodiments, outer diameter OD1 canbe at least about 0.024 inch and/or at most about 0.05 inch.

FIGS. 2A and 2B show the use of embolic coil 18 to fill and occlude ananeurysmal sac 52 formed in a wall 54 of a lumen 50 of a subject. Asshown in FIG. 2A, embolic coil system 10 is delivered into lumen 50 ofthe subject. As shown in FIG. 2B, embolic coil delivery wire 16 and arms36 and 38 are used to push embolic coil 18 out of catheter 12. When arms36 and 38 are released from catheter 12, they open up, thereby releasingembolic coil 18 into aneurysmal sac 52. Embolic coil 18 partially fillsaneurysmal sac 52 after embolic coil 18 has been pushed out of catheter12 by embolic coil delivery wire 16 and arms 36 and 38. By partiallyfilling aneurysmal sac 52, embolic coil 18 helps to occlude aneurysmalsac 52. In some embodiments, after embolic coil 18 has been deliveredinto aneurysmal sac 52, one or more additional embolic coils can bedelivered into aneurysmal sac 52.

Embolic coils can generally be used in a number of differentapplications, such as neurological applications and/or peripheralapplications. In some embodiments, embolic coils can be used to embolizea lumen of a subject (e.g., to occlude a vessel), and/or to treat ananeurysm (e.g., an intercranial aneurysm), an arteriovenous malformation(AVM), a traumatic fistula, uterine fibroids, and/or cancer (e.g.,cervical cancer). In certain embodiments, embolic coils can be used inan AAA (abdominal aortic aneurysm) application. In some embodiments,embolic coils can be used to embolize a tumor (e.g., a liver tumor),and/or can be used in transarterial chemoembolization (TACE). In certainembodiments, embolic coils can be used to occlude a lumbar artery and/orto embolize a spleen (e.g., after a portion of the spleen has ruptured).In some embodiments, embolic coils can be used in a portal veinembolization (PVE) procedure.

FIGS. 3A and 3B provide enlarged views of embolic coil delivery wire 16and arms 36 and 38. As shown in FIG. 3B, embolic coil delivery wire 16includes a wire portion 70 and a sheath 72 surrounding wire portion 70.Wire portion 70 is attached to arms 36 and 38 at the distal end 40 ofembolic coil delivery wire 16. In certain embodiments, wire portion 70can be soldered (e.g., gold soldered) to arm 36 and/or arm 38. In someembodiments, wire portion 70 can be resistance welded to arm 36 and/orarm 38.

Wire portion 70 and arms 36 and/or 38 can be formed of the same materialor different materials, such as metals (e.g., platinum) and/or metalalloys (e.g., stainless steel). In some embodiments, wire portion 70 andarms 36 and/or 38 can be formed of an iridium-platinum alloy (e.g., 10percent iridium/90 percent platinum).

In certain embodiments, sheath 72 can be formed of tetrafluoroethylene(TFE). This can, for example, cause sheath 72 to be relativelylubricious. In some embodiments, as the lubricity of sheath 72increases, the maneuverability of embolic coil delivery wire 16 withinlumen 14 of catheter 12 can also increase. Embolic coil delivery wire 16can be relatively flexible, which can reduce the likelihood ofperforation of a delivery device wall and/or a body lumen wall.

While embolic coil delivery wire 16 includes a wire portion 70surrounded by a sheath 72, in some embodiments, an embolic coil deliverywire may not include a sheath. Additionally, while embolic coil deliverywire 16 includes arms 36 and 38 that are attached to wire portion 70 atdistal end 40 of embolic coil delivery wire 16, in certain embodiments,one or more arms can be attached to an embolic coil delivery wire in adifferent location. As an example, FIG. 4 shows an embolic coil deliverywire 82 including a wire portion 83 having a distal end 84, and two arms86 and 88 extending from wire portion 83 at a location that is proximalto distal end 84. Arms 86 and 88 are directly bonded to wire portion 83.Embolic coil delivery wire 82 does not include a sheath.

FIGS. 5A and 5B show enlarged views of embolic coil 18. As shown inFIGS. 5A and 5B, peanut-shaped head 34 is rotationally symmetric about alongitudinal axis LA1 of head 34. As shown in FIG. 5B, head 34 includesan attachment region 90 to which embolic coil body 20 is attached (e.g.,welded). Head 34 and embolic coil body 20 can be formed of the samematerial or of different materials, such as metals, metal alloys, and/orpolymers. In certain embodiments in which head 34 and embolic coil body20 are formed of the same metals and/or metal alloys, head 34 andembolic coil body 20 can be relatively corrosion-resistant.

Examples of metals include platinum, tungsten, tantalum, palladium,lead, gold, titanium, and silver. Examples of metal alloys includestainless steel, alloys of tungsten, alloys of tantalum, alloys ofplatinum (e.g., platinum-tungsten alloys such as 92 percentplatinum/eight percent tungsten, platinum-iridium alloys such as 92percent platinum/eight percent iridium), alloys of palladium, alloys oflead, alloys of gold, alloys of titanium, alloys of silver, andcobalt-chromium alloys (e.g., Elgiloy® alloy, from Elgiloy SpecialtyMaterials). Examples of polymers include polyolefins, polyurethanes,block copolymers, polyethers, and polyimides. Other examples of polymersare disclosed, for example, in Buiser et al., U.S. patent applicationSer. No. 11/311,617, filed on Dec. 19, 2005, and entitled “Coils”, whichis incorporated herein by reference.

In some embodiments, it may be desirable to observe embolic coil 18using X-ray fluoroscopy. In some such embodiments, head 34 and/orembolic coil body 20 can include one or more radiopaque materials thatcan enhance the visibility of head 34 and/or embolic coil body 20 underX-ray fluoroscopy. As an example, embolic coil body 20 may be formed ofa radiopaque material. As another example, peanut-shaped head 34 may beformed of a material (e.g., a metal, a polymer) that encapsulates aradiopaque material, and/or may be formed of a material (e.g., a metal,a polymer) within which a radiopaque material is disposed. As anadditional example, peanut-shaped head 34 may include a coating of aradiopaque material.

As used herein, a radiopaque material refers to a material having adensity of about ten grams per cubic centimeter or greater (e.g., about25 grams per cubic centimeter or greater, about 50 grams per cubiccentimeter or greater). A radiopaque material can be, for example, ametal, a metal alloy, a metal oxide (e.g., titanium dioxide, zirconiumoxide, aluminum oxide), bismuth subcarbonate, or barium sulfate. In someembodiments, a radiopaque material is a radiopaque contrast agent.Examples of radiopaque contrast agents include Omnipaque™, Renocal®,iodiamide meglumine, diatrizoate meglumine, ipodate calcium, ipodatesodium, iodamide sodium, iothalamate sodium, iopamidol, and metrizamide.Radiopaque contrast agents are commercially available from, for example,Bracco Diagnostic. Radiopaque materials are described, for example, inRioux et al., U.S. Patent Application Publication No. US 2004/0101564A1, published on May 27, 2004, and entitled “Embolization”, which isincorporated herein by reference.

In some embodiments, head 34 and/or embolic coil body 20 can be formedout of one or more shape-memory materials, such as shape-memory metalalloys and/or shape-memory polymers. An example of a shape-memory metalalloy is Nitinol. Examples of shape-memory polymers include shape-memorypolyurethanes and the Veriflex™ two-part thermoset shape-memory polymerresin system (from CRG Industries, Dayton, Ohio).

In certain embodiments, head 34 and/or embolic coil body 20 can beformed of one or more bioerodible materials. Examples of bioerodiblematerials include polylactic acid (PLA), polyglycolic acid (PGA),polysaccharides (e.g., alginate), water soluble polymers (e.g.,polyvinyl alcohol, such as polyvinyl alcohol that has not beencross-linked), biodegradable poly DL-lactide-poly ethylene glycol(PELA), hydrogels (e.g., polyacrylic acid, hyaluronic acid, gelatin suchas gelatin foam, carboxymethyl cellulose), polyethylene glycol (PEG),chitosan, polyesters (e.g., polycaprolactones), poly(lactic-co-glycolic)acid (e.g., a poly(d-lactic-co-glycolic) acid), polyamino acids,polynucleic acids, polyhydroxyalkanoates, polyanhydrides, andcombinations thereof.

As shown in FIGS. 5A and 5B, embolic coil 18 in its primary shape has alength L1. In some embodiments, length L1 can be at least about twomillimeters (e.g., at least about 10 millimeters, at least about 50millimeters, at least about 100 millimeters, at least about 250millimeters) and/or at most about 500 millimeters (e.g., at most about250 millimeters, at most about 100 millimeters, at most about 50millimeters, at most about 10 millimeters).

As shown in FIG. 5B, embolic coil body 20 has an inner diameter ID2 andan outer diameter OD2. In some embodiments, inner diameter ID2 can be atleast 0.006 inch (e.g., at least 0.01 inch, at least 0.02 inch) and/orat most 0.028 inch (e.g., at most 0.02 inch, at most 0.01 inch). Incertain embodiments, outer diameter OD1 can be at least 0.01 inch (e.g.,at least 0.02 inch, at least 0.03 inch) and/or at most 0.038 inch (e.g.,at most 0.03 inch, at most 0.02 inch).

The pitch of an embolic coil body is the sum of the thickness of onewinding of wire (e.g., winding 22 of wire 28) and the amount of spacebetween that winding and a consecutive winding of wire (e.g., winding 23of wire 28). FIG. 5A shows the pitch P1 of embolic coil body 20. Becausethe windings of embolic coil body 20 are flush with each other, pitch P1of embolic coil body 20 is equal to the thickness of one winding ofembolic coil body 20. In some embodiments, pitch P1 can be at most 0.004inch and/or at least 0.002 inch.

In general, embolic coil 18 has a primary shape and a secondary shape.Embolic coil 18 exhibits only its primary shape when embolic coil 18 isextended within lumen 14 of catheter 12 (as shown in FIG. 1). As emboliccoil 18 exits catheter 12, however, embolic coil 18 further assumes itssecondary shape, which can, for example, allow embolic coil 18 to fill atarget site (e.g., an aneurysmal sac). Typically, the primary shape ofembolic coil 18 can be selected for deliverability, and the secondaryshape of embolic coil 18 can be selected for application (e.g.,embolization of an aneurysm).

As FIGS. 6-12 illustrate, an embolic coil can have any of a number ofdifferent secondary shapes, which can depend on the particularapplication for the embolic coil.

For example, FIG. 6 shows an embolic coil 100 with a spiral secondaryshape, which can be used, for example, to provide a supportive frameworkalong a vessel wall. Alternatively or additionally, an embolic coil witha spiral secondary shape can be used to hold other embolic coils thatare subsequently delivered to the target site.

FIG. 7 shows an embolic coil 110 with a single apex vortex secondaryshape, which can be used, for example, to close the center of a targetsite (e.g., a vessel, an aneurysm) that is to be occluded, and/or toocclude a target site in conjunction with an embolic coil such asembolic coil 100 (FIG. 6). An embolic coil with a single apex vortexsecondary shape can be used to occlude a vessel having low flow,intermediate flow, or high flow. In some embodiments, multiple emboliccoils with single apex vortex secondary shapes can be used to occlude avessel. In certain embodiments, an embolic coil with a single apexvortex secondary shape can be used as a packing coil, such that the coilcan be packed into a vessel that is slightly smaller than the diameterof the coil. As an example, a six-millimeter diameter coil can be packedinto a vessel having a five-millimeter diameter. In some embodiments, anembolic coil with a single apex vortex secondary shape can be used toembolize a tumor and/or to treat gastrointestinal bleeding.

As shown in FIG. 8, an embolic coil 120 can have a dual apex vortexsecondary shape (also known as a diamond secondary shape), which, likethe single apex vortex secondary shape, can used, for example, to closethe center of a target site (e.g., a vessel, an aneurysm) that is to beoccluded, and/or to occlude a target site in conjunction with an emboliccoil such as embolic coil 100 (FIG. 6). An embolic coil with a dual apexvortex secondary shape can be used to occlude a vessel having low flow,intermediate flow, or high flow, and can be used alone or in combinationwith other embolic coils (e.g., other embolic coils having dual apexvortex secondary shapes). In certain embodiments, an embolic coil with adual apex vortex secondary shape can be used as a packing coil. In someembodiments, an embolic coil with a dual apex vortex secondary shape canbe used to embolize a tumor and/or to treat gastrointestinal bleeding.

FIG. 9 shows an embolic coil 130 with a secondary shape in the form of aJ, which can be used, for example, to fill remaining space in ananeurysm that was not filled by other coils. In some embodiments, anoperator (e.g., a physician) can hook the curved portion of embolic coil130 into a coil or coil mass that has already been deployed at a targetsite, and then shape the straighter portion of coil 130 to fill thetarget site.

FIGS. 10A and 10B show an embolic coil 140 having a complex helicalsecondary shape. An embolic coil with a complex helical secondary shapecan be used, for example, to frame a target site. In certainembodiments, an embolic coil with a complex helical secondary shape canbe used as an anchoring coil that helps to hold other embolic coils inplace at a target site (e.g., thereby allowing additional embolic coilsto be packed into the target site).

FIGS. 11A and 11B show an embolic coil 150 having a helical secondaryshape. An embolic coil with a helical secondary shape can be used, forexample, as a packing coil.

FIG. 12 shows an embolic coil 160 having a straight secondary shape. Anembolic coil with a straight secondary shape can be used, for example,in a relatively small vessel (e.g., to block blood flow to a tumor).

FIG. 13 illustrates a process for forming an embolic coil (e.g., emboliccoil 18) in its primary shape, and FIGS. 14A-14C show a process forforming the secondary shape of the embolic coil.

As shown in FIG. 13, a coil-forming apparatus 200 includes a mandrel 210held by two rotatable chucks 220 and 230. A spool 240 of wire 28 isdisposed above mandrel 210, and is attached to a linear drive 260. Toform an embolic coil in its primary shape, chucks 220 and 230 areactivated so that they rotate in the direction of arrows A2 and A3,thereby rotating mandrel 210. Linear drive 260 also is activated, andmoves spool 240 in the direction of arrow A1. The rotation of mandrel210 pulls wire 28 from spool 240 at a predetermined pull-off angle, andcauses wire 28 to wrap around mandrel 210, forming a coil 270.

As FIG. 13 shows, the pull-off angle (α) is the angle between axis PA1,which is perpendicular to longitudinal axis LA2 of mandrel 210, and theportion 280 of wire 28 between spool 240 and coil 270. In someembodiments, α can be from about one degree to about six degrees (e.g.,from about 1.5 degrees to about five degrees, from about 1.5 degrees toabout 2.5 degrees, about two degrees). In certain embodiments, acontroller (e.g., a programmable logic controller) can be used tomaintain the pull-off angle in coil-forming apparatus 200. Becausemandrel 210 is rotating as it is pulling wire 28 from spool 240, andbecause linear drive 260 is moving spool 240 in the direction of arrowA1, wire 28 forms coil 270 in a primary shape around mandrel 210. Coil270 can be formed, for example, at room temperature (25° C.).

After coil 270 has been formed, chucks 220 and 230, and linear drive260, are deactivated, and portion 280 of wire 28 is cut. Mandrel 210 isthen released from chuck 220, and coil 270 is pulled off of mandrel 210.While coil 270 might lose some of its primary shape as it is pulled offof mandrel 210, coil 270 can generally return to its primary shapeshortly thereafter, because of memory imparted to coil 270 duringformation. In some embodiments, after coil 270 has been removed frommandrel 210, one or both of the ends of coil 270 can be heated andmelted to form rounder, more biocompatible (e.g., atraumatic) ends.

Mandrel 210 can be formed of, for example, a metal or a metal alloy,such as stainless steel. In some embodiments, mandrel 210 can be formedof one or more polymers, such as Teflon® (polytetrafluoroethylene) orDelrin® (polyoxymethylene). In certain embodiments, mandrel 210 can beformed of a shape-memory material, such as Nitinol.

The tension of mandrel 210 as it is held between chucks 220 and 230preferably is sufficiently high to avoid vibration of mandrel 210 duringthe winding process, and sufficiently low to avoid stretching of mandrel210 during the winding process. In some instances, significantstretching of mandrel 210 during the winding process could cause coil270 to have a smaller primary shape than desired, and/or could make itrelatively difficult to remove coil 270 from mandrel 210. In certainembodiments, the tension of mandrel 210 can be from about 100 grams toabout 1,000 grams (e.g., from about 300 grams to about 600 grams, fromabout 400 grams to about 500 grams). For example, the tension of mandrel210 can be about 506 grams.

In some embodiments, wire 28 can be wound around mandrel 210 at atension of at least about four grams (e.g., at least about five grams,at least about six grams, at least about 10 grams, at least about 22grams, at least about 27 grams, at least about 32 grams, at least about40 grams, at least about 60 grams, at least about 65 grams, at leastabout 85 grams) and/or at most about 100 grams (e.g., at most about 85grams, at most about 65 grams, at most about 60 grams, at most about 40grams, at most about 32 grams, at most about 27 grams, at most about 22grams, at most about 10 grams, at most about six grams, at most aboutfive grams).

In certain embodiments, the length of coil 270 in its primary shape andwhile under tension on mandrel 210 can be from about 10 centimeters toabout 250 centimeters (e.g., from about 50 centimeters to about 200centimeters, from about 130 centimeters to about 170 centimeters, fromabout 144 centimeters to about 153 centimeters, from about 147centimeters to about 153 centimeters). For example, the length of coil270 in its primary shape and while under tension on mandrel 210 can beabout 132 centimeters or about 147 centimeters. Coil 270 may recoil tosome extent (e.g., by at most about five centimeters) when portion 280of wire 28 is severed, such that coil 270 will be somewhat smaller onceit has been removed from mandrel 210. In some embodiments, coil 270 canhave a length of from about five centimeters to about 225 centimeters(e.g., from about 25 centimeters to about 170 centimeters, from about120 centimeters to about 140 centimeters, from about 137 centimeters toabout 140 centimeters) after being removed from mandrel 210. After coil270 has been removed from mandrel 210, coil 270 can be cut into smallercoils.

Once coil 270 has been formed in its primary shape, coil 270 can befurther shaped into a secondary shape, as shown in FIGS. 14A-14C.

FIG. 14A shows a mandrel 310 used to form the secondary shape of coil270. While mandrel 310 is shaped to form a diamond, other types ofmandrels can be used to form other secondary shapes. Mandrel 310 isformed of a diamond-shaped block 320 with grooves 330 cut into itssurface. As shown in FIGS. 14B and 14C, coil 270 in its primary shape iswrapped around mandrel 310, such that coil 270 fills grooves 330,creating the secondary shape. The ends of coil 270 are then attached(e.g., pinned) to mandrel 310, and coil 270 is heat-treated to impartmemory to coil 270. In some embodiments, coil 270 can be heat-treated ata temperature of at least about 1000° F. (e.g., at least about 1050° F.,at least about 1100° F., at least about 1150° F.), and/or at most about1200° F. (e.g., at most about 1150° F., at most about 1100° F., at mostabout 1050° F.). In certain embodiments, the heat treatment of coil 270can last for a period of from about 10 minutes to about 40 minutes(e.g., about 25 minutes). After being heat-treated, coil 270 isunwrapped from mandrel 310. The removal of coil 270 from mandrel 310allows coil 270 to reassume its secondary shape. In some embodiments,after coil 270 has been removed from mandrel 310, one or both of theends of coil 270 can be heated and melted to form rounder, morebiocompatible (e.g., atraumatic) ends.

Mandrel 310 can be formed of, for example, a metal or a metal alloy(e.g., stainless steel). In some embodiments, mandrel 310 can be formedof a plated metal or a plated metal alloy (e.g., chrome-plated stainlesssteel).

Before, during, or after the formation of the secondary shape of coil270, a head can be attached (e.g., welded) to coil 270. The head can beformed, for example, using a micromachining process and/or an etchingprocess.

Embolic coils and methods of making embolic coils are described, forexample, in Elliott et al., U.S. Patent Application Publication No. US2006/0116711 A1, published on Jun. 1, 2006, and entitled “EmbolicCoils”, which is incorporated herein by reference.

In some embodiments, an embolic coil such as embolic coil 18 can includeone or more therapeutic agents (e.g., drugs). For example, wire 28 caninclude one or more therapeutic agents (e.g., dispersed within and/orencapsulated by the material of wire 28), can be coated with one or moretherapeutic agents, and/or can be coated with one or more coatingsincluding one or more therapeutic agents. In some embodiments, thetherapeutic agents can be dispersed within, and/or encapsulated by, thecoatings. Embolic coil 18 can, for example, be used to deliver thetherapeutic agents to a target site.

In certain embodiments in which embolic coil 18 is coated by one or morecoatings including one or more therapeutic agents, the coatings caninclude one or more bioerodible and/or bioabsorbable materials. When thecoatings are eroded and/or absorbed, they can release the therapeuticagents into the body of a subject (e.g., during delivery and/or at atarget site).

In some embodiments, a therapeutic agent-coated embolic coil can includea coating (e.g., a bioerodible and/or bioabsorbable polymer coating)over the surface of the therapeutic agent. The coating can assist incontrolling the rate at which therapeutic agent is released from theembolic coil. For example, the coating can be in the form of a porousmembrane. The coating can delay an initial burst of therapeutic agentrelease. The coating can be applied by dipping or spraying the emboliccoil. The coating can include therapeutic agent or can be substantiallyfree of therapeutic agent. The therapeutic agent in the coating can bethe same as or different from a therapeutic agent on a surface layer ofthe embolic coil and/or within the embolic coil (e.g., within a wireforming the embolic coil). A polymer coating (e.g., that is bioerodibleand/or bioabsorbable) can be applied to an embolic coil surface and/orto a coated embolic coil surface in embodiments in which a highconcentration of therapeutic agent has not been applied to the emboliccoil surface or to the coated embolic coil surface.

Coatings are described, for example, in Buiser et al., U.S. patentapplication Ser. No. 11/311,617, filed on Dec. 19, 2005, and entitled“Coils”, and in DiMatteo et al., U.S. Patent Application Publication No.US 2004/0076582 A1, published on Apr. 22, 2004, and entitled “AgentDelivery Particle”, both of which are incorporated herein by reference.

In some embodiments, one or more embolic coils can be disposed in one ormore liquid therapeutic agents.

Therapeutic agents include genetic therapeutic agents, non-genetictherapeutic agents, and cells, and can be negatively charged, positivelycharged, amphoteric, or neutral. Therapeutic agents can be, for example,materials that are biologically active to treat physiologicalconditions; pharmaceutically active compounds; gene therapies; nucleicacids with and without carrier vectors (e.g., recombinant nucleic acids,DNA (e.g., naked DNA), cDNA, RNA, genomic DNA, cDNA or RNA in anon-infectious vector or in a viral vector which may have attachedpeptide targeting sequences, antisense nucleic acids (RNA, DNA));peptides (e.g., growth factor peptides, such as basic fibroblast growthfactor (bFGF)); oligonucleotides; gene/vector systems (e.g., anythingthat allows for the uptake and expression of nucleic acids); DNAchimeras (e.g., DNA chimeras which include gene sequences and encodingfor ferry proteins such as membrane translocating sequences (“MTS”) andherpes simplex virus-1 (“VP22”)); compacting agents (e.g., DNAcompacting agents); viruses; polymers; hyaluronic acid; proteins (e.g.,enzymes such as ribozymes, asparaginase); immunologic species;nonsteroidal anti-inflammatory medications; chemoagents; pain managementtherapeutics; oral contraceptives; progestins; gonadotrophin-releasinghormone agonists; chemotherapeutic agents; and radioactive species(e.g., radioisotopes, radioactive molecules). Non-limiting examples oftherapeutic agents include anti-thrombogenic agents; antioxidants;angiogenic and anti-angiogenic agents and factors; anti-proliferativeagents (e.g., agents capable of blocking smooth muscle cellproliferation); calcium entry blockers; and survival genes which protectagainst cell death (e.g., anti-apoptotic Bcl-2 family factors and Aktkinase).

Exemplary non-genetic therapeutic agents include: anti-thrombotic agentssuch as heparin, heparin derivatives, urokinase, and PPack(dextrophenylalanine proline arginine chloromethylketone);anti-inflammatory agents such as dexamethasone, prednisolone,corticosterone, budesonide, estrogen, acetyl salicylic acid,sulfasalazine and mesalamine;antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel,5-fluorouracil, cisplatin, methotrexate, doxorubicin, vinblastine,vincristine, epothilones, endostatin, angiostatin, angiopeptin,monoclonal antibodies capable of blocking smooth muscle cellproliferation, and thymidine kinase inhibitors; anesthetic agents suchas lidocaine, bupivacaine and ropivacaine; anti-coagulants such asD-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound,heparin, hirudin, antithrombin compounds, platelet receptor antagonists,anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin,prostaglandin inhibitors, platelet inhibitors and tick antiplateletfactors or peptides; vascular cell growth promoters such as growthfactors, transcriptional activators, and translational promoters;vascular cell growth inhibitors such as growth factor inhibitors (e.g.,PDGF inhibitor-Trapidil), growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, bifunctional molecules consisting of a growth factor and acytotoxin, bifunctional molecules consisting of an antibody and acytotoxin; protein kinase and tyrosine kinase inhibitors (e.g.,tyrphostins, genistein, quinoxalines); prostacyclin analogs;cholesterol-lowering agents; angiopoietins; antimicrobial agents such astriclosan, cephalosporins, aminoglycosides and nitrofurantoin; cytotoxicagents, cytostatic agents and cell proliferation affectors; vasodilatingagents; and agents that interfere with endogenous vasoactive mechanisms.

Exemplary genetic therapeutic agents include: anti-sense DNA and RNA;DNA coding for anti-sense RNA, tRNA or rRNA to replace defective ordeficient endogenous molecules, angiogenic factors including growthfactors such as acidic and basic fibroblast growth factors, vascularendothelial growth factor, epidermal growth factor, transforming growthfactor α and β, platelet-derived endothelial growth factor,platelet-derived growth factor, tumor necrosis factor a, hepatocytegrowth factor, and insulin like growth factor, cell cycle inhibitorsincluding CD inhibitors, thymidine kinase (“TK”) and other agents usefulfor interfering with cell proliferation, and the family of bonemorphogenic proteins (“BMP's”), including BMP2, BMP3, BMP4, BMP5, BMP6(Vgr1), BMP7 (OP1), BMP8, BMP9, BMP10, BM11, BMP12, BMP13, BMP14, BMP15,and BMP16. Currently preferred BMP's are any of BMP2, BMP3, BMP4, BMP5,BMP6 and BMP7. These dimeric proteins can be provided as homodimers,heterodimers, or combinations thereof, alone or together with othermolecules. Alternatively or additionally, molecules capable of inducingan upstream or downstream effect of a BMP can be provided. Suchmolecules include any of the “hedgehog” proteins, or the DNA's encodingthem. Vectors of interest for delivery of genetic therapeutic agentsinclude: plasmids; viral vectors such as adenovirus (AV),adenoassociated virus (AAV) and lentivirus; and non-viral vectors suchas lipids, liposomes and cationic lipids.

Cells include cells of human origin (autologous or allogeneic),including stem cells, or from an animal source (xenogeneic), which canbe genetically engineered if desired to deliver proteins of interest.

Several of the above and numerous additional therapeutic agentsappropriate for the practice of the present invention are disclosed inKunz et al., U.S. Pat. No. 5,733,925, assigned to NeoRx Corporation,which is incorporated herein by reference. Therapeutic agents disclosedin this patent include the following:

“Cytostatic agents” (i.e., agents that prevent or delay cell division inproliferating cells, for example, by inhibiting replication of DNA or byinhibiting spindle fiber formation). Representative examples ofcytostatic agents include modified toxins, methotrexate, adriamycin,radionuclides (e.g., such as disclosed in Fritzberg et al., U.S. Pat.No. 4,897,255), protein kinase inhibitors, including staurosporin, aprotein kinase C inhibitor of the following formula:

as well as diindoloalkaloids having one of the following generalstructures:

as well as stimulators of the production or activation of TGF-beta,including Tamoxifen and derivatives of functional equivalents (e.g.,plasmin, heparin, compounds capable of reducing the level orinactivating the lipoprotein Lp(a) or the glycoproteinapolipoprotein(a)) thereof, TGF-beta or functional equivalents,derivatives or analogs thereof, suramin, nitric oxide releasingcompounds (e.g., nitroglycerin) or analogs or functional equivalentsthereof, paclitaxel or analogs thereof (e.g., taxotere), inhibitors ofspecific enzymes (such as the nuclear enzyme DNA topoisomerase II andDNA polymerase, RNA polymerase, adenyl guanyl cyclase), superoxidedismutase inhibitors, terminal deoxynucleotidyl-transferase, reversetranscriptase, antisense oligonucleotides that suppress smooth musclecell proliferation and the like. Other examples of “cytostatic agents”include peptidic or mimetic inhibitors (i.e., antagonists, agonists, orcompetitive or non-competitive inhibitors) of cellular factors that may(e.g., in the presence of extracellular matrix) trigger proliferation ofsmooth muscle cells or pericytes: e.g., cytokines (e.g., interleukinssuch as IL-1), growth factors (e.g., PDGF, TGF-alpha or -beta, tumornecrosis factor, smooth muscle- and endothelial-derived growth factors,i.e., endothelin, FGF), homing receptors (e.g., for platelets orleukocytes), and extracellular matrix receptors (e.g., integrins).Representative examples of useful therapeutic agents in this category ofcytostatic agents addressing smooth muscle proliferation include:subfragments of heparin, triazolopyrimidine (trapidil; a PDGFantagonist), lovastatin, and prostaglandins E1 or 12.

Agents that inhibit the intracellular increase in cell volume (i.e., thetissue volume occupied by a cell), such as cytoskeletal inhibitors ormetabolic inhibitors. Representative examples of cytoskeletal inhibitorsinclude colchicine, vinblastin, cytochalasins, paclitaxel and the like,which act on microtubule and microfilament networks within a cell.Representative examples of metabolic inhibitors include staurosporin,trichothecenes, and modified diphtheria and ricin toxins, Pseudomonasexotoxin and the like. Trichothecenes include simple trichothecenes(i.e., those that have only a central sesquiterpenoid structure) andmacrocyclic trichothecenes (i.e., those that have an additionalmacrocyclic ring), e.g., a verrucarins or roridins, including VerrucarinA, Verrucarin B, Verrucarin J (Satratoxin C), Roridin A, Roridin C,Roridin D, Roridin E (Satratoxin D), Roridin H.

Agents acting as an inhibitor that blocks cellular protein synthesisand/or secretion or organization of extracellular matrix (i.e., an“anti-matrix agent”). Representative examples of “anti-matrix agents”include inhibitors (i.e., agonists and antagonists and competitive andnon-competitive inhibitors) of matrix synthesis, secretion and assembly,organizational cross-linking (e.g., transglutaminases cross-linkingcollagen), and matrix remodeling (e.g., following wound healing). Arepresentative example of a useful therapeutic agent in this category ofanti-matrix agents is colchicine, an inhibitor of secretion ofextracellular matrix. Another example is tamoxifen for which evidenceexists regarding its capability to organize and/or stabilize as well asdiminish smooth muscle cell proliferation following angioplasty. Theorganization or stabilization may stem from the blockage of vascularsmooth muscle cell maturation in to a pathologically proliferating form.

Agents that are cytotoxic to cells, particularly cancer cells. Preferredagents are Roridin A, Pseudomonas exotoxin and the like or analogs orfunctional equivalents thereof. A plethora of such therapeutic agents,including radioisotopes and the like, have been identified and are knownin the art. In addition, protocols for the identification of cytotoxicmoieties are known and employed routinely in the art.

A number of the above therapeutic agents and several others have alsobeen identified as candidates for vascular treatment regimens, forexample, as agents targeting restenosis. Such agents include one or moreof the following: calcium-channel blockers, including benzothiazapines(e.g., diltiazem, clentiazem); dihydropyridines (e.g., nifedipine,amlodipine, nicardapine); phenylalkylamines (e.g., verapamil); serotoninpathway modulators, including 5-HT antagonists (e.g., ketanserin,naftidrofuryl) and 5-HT uptake inhibitors (e.g., fluoxetine); cyclicnucleotide pathway agents, including phosphodiesterase inhibitors (e.g.,cilostazole, dipyridamole), adenylate/guanylate cyclase stimulants(e.g., forskolin), and adenosine analogs; catecholamine modulators,including α-antagonists (e.g., prazosin, bunazosine), β-antagonists(e.g., propranolol), and α/β-antagonists (e.g., labetalol, carvedilol);endothelin receptor antagonists; nitric oxide donors/releasingmolecules, including organic nitrates/nitrites (e.g., nitroglycerin,isosorbide dinitrate, amyl nitrite), inorganic nitroso compounds (e.g.,sodium nitroprusside), sydnonimines (e.g., molsidomine, linsidomine),nonoates (e.g., diazenium diolates, NO adducts of alkanediamines),S-nitroso compounds, including low molecular weight compounds (e.g.,S-nitroso derivatives of captopril, glutathione and N-acetylpenicillamine) and high molecular weight compounds (e.g., S-nitrosoderivatives of proteins, peptides, oligosaccharides, polysaccharides,synthetic polymers/oligomers and natural polymers/oligomers),C-nitroso-, O-nitroso- and N-nitroso-compounds, and L-arginine; ACEinhibitors (e.g., cilazapril, fosinopril, enalapril); ATII-receptorantagonists (e.g., saralasin, losartin); platelet adhesion inhibitors(e.g., albumin, polyethylene oxide); platelet aggregation inhibitors,including aspirin and thienopyridine (ticlopidine, clopidogrel) and GPIIb/IIIa inhibitors (e.g., abciximab, epitifibatide, tirofiban,intergrilin); coagulation pathway modulators, including heparinoids(e.g., heparin, low molecular weight heparin, dextran sulfate,β-cyclodextrin tetradecasulfate), thrombin inhibitors (e.g., hirudin,hirulog, PPACK (D-phe-L-propyl-L-arg-chloromethylketone), argatroban),FXa inhibitors (e.g., antistatin, TAP (tick anticoagulant peptide)),vitamin K inhibitors (e.g., warfarin), and activated protein C;cyclooxygenase pathway inhibitors (e.g., aspirin, ibuprofen,flurbiprofen, indomethacin, sulfinpyrazone); natural and syntheticcorticosteroids (e.g., dexamethasone, prednisolone, methprednisolone,hydrocortisone); lipoxygenase pathway inhibitors (e.g.,nordihydroguairetic acid, caffeic acid; leukotriene receptorantagonists; antagonists of E- and P-selectins; inhibitors of VCAM-1 andICAM-1 interactions; prostaglandins and analogs thereof, includingprostaglandins such as PGE1 and PGI2; prostacyclin analogs (e.g.,ciprostene, epoprostenol, carbacyclin, iloprost, beraprost); macrophageactivation preventers (e.g., bisphosphonates); HMG-CoA reductaseinhibitors (e.g., lovastatin, pravastatin, fluvastatin, simvastatin,cerivastatin); fish oils and omega-3-fatty acids; free-radicalscavengers/antioxidants (e.g., probucol, vitamins C and E, ebselen,retinoic acid (e.g., trans-retinoic acid), SOD mimics); agents affectingvarious growth factors including FGF pathway agents (e.g., bFGFantibodies, chimeric fusion proteins), PDGF receptor antagonists (e.g.,trapidil), IGF pathway agents (e.g., somatostatin analogs such asangiopeptin and ocreotide), TGF-β pathway agents such as polyanionicagents (heparin, fucoidin), decorin, and TGF-β antibodies, EGF pathwayagents (e.g., EGF antibodies, receptor antagonists, chimeric fusionproteins), TNF-α pathway agents (e.g., thalidomide and analogs thereof),thromboxane A2 (TXA2) pathway modulators (e.g., sulotroban, vapiprost,dazoxiben, ridogrel), protein tyrosine kinase inhibitors (e.g.,tyrphostin, genistein, and quinoxaline derivatives); MMP pathwayinhibitors (e.g., marimastat, ilomastat, metastat), and cell motilityinhibitors (e.g., cytochalasin B); antiproliferative/antineoplasticagents including antimetabolites such as purine analogs (e.g.,6-mercaptopurine), pyrimidine analogs (e.g., cytarabine and5-fluorouracil) and methotrexate, nitrogen mustards, alkyl sulfonates,ethylenimines, antibiotics (e.g., daunorubicin, doxorubicin, daunomycin,bleomycin, mitomycin, penicillins, cephalosporins, ciprofalxin,vancomycins, aminoglycosides, quinolones, polymyxins, erythromycins,tertacyclines, chloramphenicols, clindamycins, linomycins, sulfonamides,and their homologs, analogs, fragments, derivatives, and pharmaceuticalsalts), nitrosoureas (e.g., carmustine, lomustine) and cisplatin, agentsaffecting microtubule dynamics (e.g., vinblastine, vincristine,colchicine, paclitaxel, epothilone), caspase activators, proteasomeinhibitors, angiogenesis inhibitors (e.g., endostatin, angiostatin andsqualamine), and rapamycin, cerivastatin, flavopiridol and suramin;matrix deposition/organization pathway inhibitors (e.g., halofuginone orother quinazolinone derivatives, tranilast); endothelializationfacilitators (e.g., VEGF and RGD peptide); and blood rheology modulators(e.g., pentoxifylline).

Other examples of therapeutic agents include anti-tumor agents, such asdocetaxel, alkylating agents (e.g., mechlorethamine, chlorambucil,cyclophosphamide, melphalan, ifosfamide), plant alkaloids (e.g.,etoposide), inorganic ions (e.g., cisplatin), biological responsemodifiers (e.g., interferon), and hormones (e.g., tamoxifen, flutamide),as well as their homologs, analogs, fragments, derivatives, andpharmaceutical salts.

Additional examples of therapeutic agents include organic-solubletherapeutic agents, such as mithramycin, cyclosporine, and plicamycin.Further examples of therapeutic agents include pharmaceutically activecompounds, anti-sense genes, viral, liposomes and cationic polymers(e.g., selected based on the application), biologically active solutes(e.g., heparin), prostaglandins, prostcyclins, L-arginine, nitric oxide(NO) donors (e.g., lisidomine, molsidomine, NO-protein adducts,NO-polysaccharide adducts, polymeric or oligomeric NO adducts orchemical complexes), enoxaparin, Warafin sodium, dicumarol, interferons,chymase inhibitors (e.g., Tranilast), ACE inhibitors (e.g., Enalapril),serotonin antagonists, 5-HT uptake inhibitors, and beta blockers, andother antitumor and/or chemotherapy drugs, such as BiCNU, busulfan,carboplatinum, cisplatinum, cytoxan, DTIC, fludarabine, mitoxantrone,velban, VP-16, herceptin, leustatin, navelbine, rituxan, and taxotere.

Therapeutic agents are described, for example, in Buiser et al., U.S.patent application Ser. No. 11/311,617, filed on Dec. 19, 2005, andentitled “Coils”; DiMatteo et al., U.S. Patent Application PublicationNo. US 2004/0076582 A1, published on Apr. 22, 2004, and entitled “AgentDelivery Particle”; Pinchuk et al., U.S. Pat. No. 6,545,097; and Schwarzet al., U.S. Pat. No. 6,368,658, all of which are incorporated herein byreference.

While certain embodiments have been described, other embodiments arepossible.

As an example, in some embodiments, an embolic coil can have at leasttwo arms extending from it, and in certain embodiments, an embolic coildelivery wire can have a non-hook-shaped head (e.g., a peanut-shapedhead). For example, FIG. 15A shows an embolic coil system 350 includinga catheter 352 with a lumen 354. Embolic coil system 350 also includesan embolic coil delivery wire 356 and an embolic coil 362 disposedwithin lumen 354. Embolic coil delivery wire 356 includes apeanut-shaped head 360, and embolic coil 362 includes arms 364 and 366extending from it. Arms 364 and 366 are detachably engaged with head 360of embolic coil delivery wire 356.

FIGS. 15B and 15C show enlarged views of embolic coil delivery wire 356.As shown in FIG. 15C, embolic coil delivery wire 356 includes a wireportion 368 surrounded by a sheath 370. Wire portion 368 is connected tohead 360. However, in some embodiments, a wire portion can be integrallyformed with a non-hook-shaped head.

FIGS. 15D and 15E show enlarged views of embolic coil 362. As shown inFIG. 15E, arms 364 and 366 are integrally formed with an attachmentportion 372 that is attached to embolic coil body 361 of embolic coil362.

As another example, while embolic coils and embolic coil delivery wireswith two arms extending from them have been described, in someembodiments, more than two arms (e.g., three arms, four arms, five arms,10 arms, 16 arms) can extend from an embolic coil or an embolic coildelivery wire.

As a further example, while embolic coils and embolic coil deliverywires with peanut-shaped heads have been described, in some embodiments,an embolic coil or an embolic coil delivery wire can have a head that isnot peanut-shaped. For example, in certain embodiments, an embolic coilor an embolic coil delivery wire can have a conical head.

As an additional example, while embolic coils and embolic coil deliverywires with heads that are rotationally symmetric about a longitudinalaxis have been described, in some embodiments, an embolic coil or anembolic coil delivery wire can have a head that is not rotationallysymmetric about a longitudinal axis. In certain embodiments, an emboliccoil or an embolic coil delivery wire can have a head that is notrotationally symmetric about any axis.

As another example, in some embodiments, an embolic coil or an emboliccoil delivery wire can have a head including a lumen. This can, forexample, allow fluids (e.g., contrast agent, saline solution) to flowthrough the head during delivery and/or use of the embolic coil orembolic coil delivery wire.

As an additional example, in certain embodiments, an embolic coil or anembolic coil delivery wire can include a head having one or more groovesin it. For example, FIG. 16 shows an embolic coil system 400 includingan embolic coil delivery wire 402 with arms 404 and 406 extending fromit, and an embolic coil 408 having a head 410. Head 410 includes ahelical groove 412 on its surface 414. The tip 416 of arm 404 and thetip 418 of arm 406 each are disposed within groove 412. The presence ofgroove 412 on head 410 can, for example, enhance the engagement of arms404 and 406 with head 410.

As a further example, in some embodiments, an embolic coil can includean embolic coil body and one or more arms that are integrally formedwith the embolic coil body. For example, FIG. 17 shows an embolic coilsystem 450 including a catheter 452 having a lumen 454, an embolic coildelivery wire 456 having a head 458, and an embolic coil 460 includingtwo arms 462 and 464 that are detachably engaged with head 458. Emboliccoil 460 is formed of two coiled wires 466 and 468 that are co-woundwith each other. Arm 462 is formed from an end of coiled wire 466, andarm 464 is formed from an end of coiled wire 468.

As another example, while arms have been described as being used toengage an embolic coil with an embolic coil delivery wire, in certainembodiments, one or more other devices can be used to engage an emboliccoil with an embolic coil delivery wire. For example, FIG. 18A shows anembolic coil system 500 including a catheter 501 having a lumen 502, andan embolic coil delivery wire 504 and an embolic coil 506 disposed inlumen 502. Embolic coil delivery wire 504 has a tubular mesh member 508in its distal section 510. Tubular mesh member 508 is engaged with ahead 512 of an embolic coil 506. Catheter 501 helps to restrain tubularmesh member 508. As shown in FIG. 18B, when embolic coil delivery wire504 is pushed in the direction of arrow A4, tubular mesh member 508exits catheter 501 and opens up. As shown in FIG. 18C, when tubular meshmember 508 has opened up sufficiently, tubular mesh member 508 releasesembolic coil 506. Tubular mesh member 508 can be formed of, for example,one or more metals (e.g., platinum) and/or metal alloys (e.g., stainlesssteel, cobalt-chromium alloys such as Elgiloy®). In certain embodiments,tubular mesh member 508 can be formed of tantalum-cored wire. This can,for example, result in tubular mesh member 508 being sufficientlyradiopaque to be viewed using X-ray fluoroscopy.

In some embodiments, an embolic coil delivery wire including a tubularmesh member can be disposed within a lumen of a sheath that, in turn, isdisposed within a lumen of a catheter. The embolic coil delivery wirecan be used to deliver an embolic coil by pushing the embolic coildelivery wire distally and withdrawing the sheath proximally, therebyexposing the tubular mesh member and releasing the embolic coil.

In certain embodiments, an embolic coil delivery wire can include atubular mesh member that is engaged with an embolic coil (e.g., a headof an embolic coil), and when the tubular mesh member and the emboliccoil are unconstrained by a delivery device, the tubular mesh member canhave a retention strength that is less than the flexural spring strengthof the embolic coil. The result can be that the tubular mesh memberdisengages from the embolic coil, thereby deploying the embolic coil.

As an additional example, in certain embodiments, an embolic coil caninclude fibers. For example, FIG. 19 shows embolic coil 600 including apeanut-shaped head 602, an embolic coil body 604, and fibers 606 tightlyfitted between consecutive windings (e.g., windings 608 and 610) ofembolic coil body 604. In some embodiments in which an embolic coilincludes fibers, the occlusion of a target site by the embolic coil canbe accelerated by the fibers, which can enhance thrombosis at the targetsite. An accelerated embolization procedure can benefit the subject by,for example, reducing exposure time to fluoroscopy.

Fibers 606 typically can be made of one or more materials that canenhance thrombosis (e.g., at a target site). In some embodiments, fibers606 can be made of one or more polyesters and/or polyamides. Examples ofmaterials from which fibers 606 can be made include polyethyleneterephthalate (e.g., Dacron®), nylon, and collagen. In certainembodiments, fibers 606 can have a length of from about 0.5 millimeterto about five millimeters (e.g., about 2.5 millimeters).

While FIG. 19 shows bunches of fibers 606 that are all separated fromtheir neighboring bunches of fibers 606 by the same number of windings,in some embodiments, an embolic coil can have a different configurationof fibers. For example, in certain embodiments, an embolic coil can haveonly one bunch of fibers, or can have bunches of fibers that areseparated from their neighboring bunches of fibers by different numbersof windings. As an example, one bunch of fibers on an embolic coil maybe separated from a neighboring bunch of fibers by three windings, whileanother bunch of fibers on the embolic coil is separated from aneighboring bunch of fibers by five windings.

In some embodiments, a fibered embolic coil such as embolic coil 600 canbe formed as follows. After the embolic coil has been formed into itssecondary shape, fibers can be attached to the embolic coil. In someembodiments, an embolic coil can be stretched prior to attaching fibersto the embolic coil, so that the embolic coil is in its extended primaryshape, and can then be loaded onto a fibering mandrel (e.g., a fiberingmandrel from Sematool Mold and Die Co., Santa Clara, Calif.). In certainembodiments, fibers can be snapped between windings of an embolic coil.In some embodiments, fibers can be tied to windings of an embolic coiland/or wrapped around windings of an embolic coil. In certainembodiments, fibers can be bonded (e.g., adhesive bonded) to windings ofan embolic coil. In some embodiments, one portion (e.g., one end) of abunch of fibers can be snapped in between windings in one region of anembolic coil, and another portion (e.g., the other end) of the samebunch of fibers can be wrapped around part of the embolic coil andsnapped in between windings in another region of the embolic coil.

As a further example, in some embodiments, an embolic coil can have atleast two regions (e.g., three, four, five, 10, 15, 20) with differentouter diameters. Embolic coils including regions with different outerdiameters are described, for example, in Elliott et al., U.S. PatentApplication Publication No. US 2006/0116711 A1, published on Jun. 1,2006, and entitled “Embolic Coils”, and Buiser et al., U.S. patentapplication Ser. No. 11/430,602, filed on May 9, 2006, and entitled“Embolic Coils”, both of which are incorporated herein by reference.

As another example, while embodiments have been shown in which the pitchof an embolic coil is substantially the same in different regions of theembolic coil, in certain embodiments, the pitch of an embolic coil candiffer in different regions of the embolic coil. For example, someregions of an embolic coil can have a pitch of 0.002 inch, while otherregions of an embolic coil can have a pitch of 0.004 inch.

As an additional example, in some embodiments, an embolic coil deliverywire can be temporarily attached to an embolic coil by one or morebioerodible connectors. For example, in certain embodiments, an emboliccoil delivery wire can have one or more arms extending from it, and thearms can be connected to an embolic coil (e.g., a head of an emboliccoil) by one or more bioerodible connectors.

As a further example, in some embodiments, an embolic coil can bedelivered to a target site by electrolytically detaching the emboliccoil from an embolic coil delivery wire. For example, FIG. 20 shows anembolic coil system 700 including a catheter 702 having a lumen 704, andan embolic coil delivery wire 706 and an embolic coil 708 disposed inlumen 704. Embolic coil delivery wire 706 includes two arms 710 and 712that are detachably engaged with a head 714 of embolic coil 708. Arms710 and 712 include insulated portions 716 and 718, and metal portions720 and 722 that are welded to head 714. Metal portions 720 and 722 areelectrolytically detachable from head 714. Electrolytic detachment isdescribed, for example, in Guglielmi et al., U.S. Pat. No. 5,895,385,which is incorporated herein by reference.

As an additional example, in some embodiments, an embolic coil deliverywire can include arms that are connected directly to an embolic coilbody of an embolic coil. For example, FIG. 21 shows an embolic coilsystem 750 including an embolic coil delivery wire 752 having arms 754and 756, and an embolic coil 758 including an embolic coil body 760.Arms 754 and 756 are connected directly to embolic coil body 760. Incertain embodiments, embolic coil 758 can be delivered to a target siteby electrolytically detaching embolic coil body 760 from arms 754 and756.

As another example, in some embodiments, multiple (e.g., two, three,four) embolic coils can be delivered using one delivery device.

As an additional example, in certain embodiments, a treatment site canbe occluded by using embolic coils in conjunction with other occlusivedevices. For example, embolic coils can be used with embolic particlessuch as those described in Buiser et al., U.S. Patent ApplicationPublication No. US 2003/0185896 A1, published on Oct. 2, 2003, andentitled “Embolization”, and in Lanphere et al., U.S. Patent ApplicationPublication No. US 2004/0096662 A1, published on May 20, 2004, andentitled “Embolization”, both of which are incorporated herein byreference. In some embodiments, embolic coils can be used in conjunctionwith one or more embolic gels. Embolic gels are described, for example,in Richard et al., U.S. Patent Application Publication No. US2006/0045900 A1, published on Mar. 2, 2006, and entitled “Embolization”,which is incorporated herein by reference.

As another example, in certain embodiments, an embolic coil can beloaded into a delivery device using an introducer sheath. For example,FIG. 22 illustrates the transfer of an embolic coil 800 from anintroducer sheath 810 into a catheter 820. A hub 830 located at theproximal end 840 of catheter 820 directs the placement of introducersheath 810. After introducer sheath 810 has been placed in hub 830, anembolic coil delivery wire 850, having two arms 860 and 870 that aredetachably engaged with a head 880 of embolic coil 800, is used to pushembolic coil 800 out of introducer sheath 810 and into catheter 820.

As an additional example, in some embodiments, an embolic coil caninclude one or more radiopaque markers. The radiopaque markers can, forexample, be attached to one or more windings of the embolic coil.

As a further example, in certain embodiments, an end of an embolic coilcan be heated and melted to make the end rounder and/or morebiocompatible (e.g., atraumatic).

As another example, in some embodiments, an embolic coil can be formedof windings of a ribbon. Embolic coils that are formed of windings of aribbon are described, for example, in Buiser et al., U.S. patentapplication Ser. No. 11/430,602, filed on May 9, 2006, and entitled“Embolic Coils”, which is incorporated herein by reference.

Other embodiments are in the claims.

What is claimed is:
 1. A system for treating a patient, comprising: a catheter having a proximal end, a distal end, and a lumen extending from the proximal end to the distal end; a delivery wire slidably disposed within the lumen, the delivery wire having a proximal end and a distal end; and an embolic device having a proximal and a distal end, wherein (a) the proximal end of the embolic device includes a structure expandable between first and second positions relative to the distal end of the catheter, (b) the distal end of the delivery wire includes a head with a helical groove on the outer surface of the head configured for enhanced engagement with the structure, (c) the structure interfits with the head when in the first position, and (d) the structure assumes the second position when the proximal end of the embolic device is positioned distally to the lumen of the catheter.
 2. The system of claim 1, wherein the head is peanut shaped.
 3. The system of claim 1, wherein the structure includes a tubular mesh.
 4. The system of claim 1, wherein the head is conical.
 5. The system of claim 1, wherein the head is not rotationally symmetrical about a longitudinal axis.
 6. The system of claim 1, wherein the head is not rotationally symmetrical about any axis.
 7. The system of claim 1, wherein the head includes a radiopaque marker.
 8. The system of claim 1, wherein the structures are configured to flex such that the proximal end of the embolic device can be inserted into a catheter having an inner diameter of between 0.018 inches and 0.035 inches.
 9. The system of claim 1, wherein the structure includes two, three, five, ten or sixteen arms.
 10. A system for treating a patient, comprising: a catheter having a proximal end, a distal end, and a lumen extending from the proximal end to the distal end; a delivery wire slidably disposed within the lumen, the delivery wire having a proximal end and a distal end; and an embolic device having a proximal end and a distal end, wherein (a) the proximal end of the embolic device includes a plurality of arms expandable between first and second configurations, (b) the distal end of the delivery wire includes a head with a helical groove on the outer surface of the head configured for enhanced engagement with the plurality of arms, (c) the arms form an interference fit with the head when in the first configuration, and (d) the arms assume the second configuration when the proximal end of the embolic device is positioned distally relative to the catheter lumen.
 11. The system of claim 10, wherein the head is peanut shaped.
 12. The system of claim 10, wherein the structure includes a tubular mesh.
 13. The system of claim 10, wherein the head is conical.
 14. The system of claim 10, wherein the head is not rotationally symmetrical about a longitudinal axis.
 15. The system of claim 10, wherein the head is not rotationally symmetrical about any axis.
 16. The system of claim 10, wherein the head includes a radiopaque marker.
 17. The system of claim 16, wherein the arms are configured to flex such that the proximal end of the embolic device can be inserted into a catheter having an inner diameter of between 0.018 inches and 0.035 inches.
 18. The system of claim 9, wherein the arms include two, three, five, ten or sixteen arms.
 19. A method of treating a patient, comprising: inserting a system comprising a catheter, a delivery wire and an embolic device into a body lumen of a patient; positioning a distal end of the catheter at a position within the body lumen where embolization is required; and moving the catheter relative to the delivery wire so that a distal end of the delivery wire exits a lumen of the catheter, thereby releasing a proximal end of the embolic device from a distal end of the delivery wire.
 20. The method of claim 19, wherein the embolic device includes a first configuration when disposed within the lumen of the catheter and a second configuration different than the first configuration upon exiting the lumen of the catheter. 